DESCRIPTION (provided by investigator): The lack of reliable wide-spectrum antibiotics and rapid emergence of antibiotic resistance in dangerous pathogens poses immediate threats for human health generally and major biodefense concerns. Novel classes of antimicrobial compounds uncompromised by resistance and targeting highly conserved, functionally critical molecular sites in bacteria are urgently needed. Elongation Factor Tu (EF-Tu) is an optimal target for broadly reactive antimicrobials: EF-Tu has at least three functionally relevant binding pockets essentially identical among many bacterial species, including E. coli, S. typhimurium and S. flexneri, V. cholerae, and plague agent Yersinia Pestis. Recently solved by Dr. Frances Jurnak, UC-Irvine, the 3D structures of EF-Tu protein co-crystallized with natural antibiotics explain the atomic details of inhibitor activity of these molecules and provide a solid basis for rational design of new, safe and effective antimicrobials. Our application combines Dr. Jurnak's structural studies with Molsoft's state of the art flexible docking and virtual ligand screening capabilities, and Chemical Diversity Laboratories' expertise in parallel synthesis, biochemical and biological assays to discover new antibiotics in a rapid, structure-focused manner.